Acute Radiation EffectsAcute Radiation Effects

Acute Radiation EffectsAcute Radiation Effects

Human data generated primarily from:Human data generated primarily from:

Atom Bomb survivorsAtom Bomb survivors

Marshallese accident victimsMarshallese accident victims

Accidents at nuclear installations, e.g., Accidents at nuclear installations, e.g., ChernobylChernobyl

Acute Radiation EffectsAcute Radiation Effects

The Radiation Accident Registry maintained by the The Radiation Accident Registry maintained by the Radiation Emergency Assistance Center at Oak Ridge Radiation Emergency Assistance Center at Oak Ridge National Library has documented 403 radiation National Library has documented 403 radiation accidents from 1944accidents from 1944--19991999

Of these, 19 involved nuclear reactors, 303 involved Of these, 19 involved nuclear reactors, 303 involved radiation devices, and 81 isotopesradiation devices, and 81 isotopes

Resulted in 120 deaths; 30 in the US, 2 in GB, 32 in Resulted in 120 deaths; 30 in the US, 2 in GB, 32 in the former USSRthe former USSR

Prodromal Radiation SyndromeProdromal Radiation SyndromeRefers to early symptoms seen after exposure to highRefers to early symptoms seen after exposure to high--intensity radiation intensity radiation

Vary with respect to time of onset, severity, and Vary with respect to time of onset, severity, and duration duration

Doses of ~ 30 Gy individuals will exhibit all phases Doses of ~ 30 Gy individuals will exhibit all phases of the syndrome within 5of the syndrome within 5--15 min of exposure 15 min of exposure

Severe prodromal syndrome usually associated with Severe prodromal syndrome usually associated with poor prognosispoor prognosis

Prodromal Radiation SyndromeProdromal Radiation Syndrome

Signs and symptoms divided into 2 main groupsSigns and symptoms divided into 2 main groups

A.A. GastrointestinalGastrointestinal: : anorexia, nausea, vomiting etc.anorexia, nausea, vomiting etc.

B.B. NeuromuscularNeuromuscular: : easy fatigability, fever, and hypotension.easy fatigability, fever, and hypotension.

Prodromal Radiation SyndromeProdromal Radiation Syndrome

Hypotension

Immediate diarrheaFeverAdditional Signs to be expected after Supralethal Doses

Vomiting

AnorexiaEasy fatigabilitySigns and Symptoms to be expected at ~ 50% Lethal Dose

GastrointestinalNeuromuscular

Characteristics of Prodromal and Latency Characteristics of Prodromal and Latency Periods as Function of DosePeriods as Function of Dose

2-4 days48Minutes to 1>5.5

1-2.5 weeks241-23.5-5.5

2-3 weeks12-242-62.0-3.5

3 weeks or longer

Cerebrovascular SyndromeCerebrovascular SyndromeTotal body dose of approx. 100 Gy Total body dose of approx. 100 Gy γγ rays will cause death in a rays will cause death in a

few hoursfew hours

N.B. All organs severely damaged and would cause death if the N.B. All organs severely damaged and would cause death if the person survived long enoughperson survived long enough

Cerebrovascular damage occurs rapidly, causing death within Cerebrovascular damage occurs rapidly, causing death within 2424--48h. See severe nausea and vomiting within minutes, 48h. See severe nausea and vomiting within minutes, followed by disorientation, respiratory distress, diarrhea, followed by disorientation, respiratory distress, diarrhea, seizures, coma, and death seizures, coma, and death

Pathogenesis thought to be massive edema leading to severe Pathogenesis thought to be massive edema leading to severe brain dysfunctionbrain dysfunction

Cerebrovascular SyndromeCerebrovascular Syndrome1964: 38 year1964: 38 year--oldold--man working in a man working in a 235235U recovery plant U recovery plant

was involved in nuclear accident; received total dose was involved in nuclear accident; received total dose of ~88 Gy (22 Gy neutrons, 66 Gy of ~88 Gy (22 Gy neutrons, 66 Gy γγ rays)rays)

Recalled seeing a flash, hurled backwards but did not Recalled seeing a flash, hurled backwards but did not lose consciousness. Ran from scene of accident to lose consciousness. Ran from scene of accident to another building 200 yards awayanother building 200 yards away

Complained of abdominal cramps and headaches, Complained of abdominal cramps and headaches, vomited, was incontinent with bloody diarrheal vomited, was incontinent with bloody diarrheal stools. Next day patient comfortable but restlessstools. Next day patient comfortable but restless

Cerebrovascular SyndromeCerebrovascular Syndrome

On second day condition deterioratedOn second day condition deteriorated

Victim became restless, fatigued, apprehensive, short Victim became restless, fatigued, apprehensive, short of breath, greatly impaired vision, hypotensiveof breath, greatly impaired vision, hypotensive

Six hours before death became disoriented, blood Six hours before death became disoriented, blood pressure could not be maintainedpressure could not be maintained

Died 49 h after accidentDied 49 h after accident

Gastrointestinal SyndromeGastrointestinal Syndrome

Total body exposure of approx.10 Gy Total body exposure of approx.10 Gy γγ rays leads to the rays leads to the GI syndromeGI syndrome

Symptoms: nausea, vomiting and severe diarrheaSymptoms: nausea, vomiting and severe diarrhea

Seen within 3Seen within 3--10 days of irradiation. Prolonged 10 days of irradiation. Prolonged diarrhea indicates poor prognosis, with death diarrhea indicates poor prognosis, with death occurring in a few days occurring in a few days

No human has survived a dose of >10 GyNo human has survived a dose of >10 Gy

Mechanism of Gastrointestinal Mechanism of Gastrointestinal SyndromeSyndrome

Hematopoietic SyndromeHematopoietic SyndromeTotal body exposure of 3Total body exposure of 3--8 Gy leads to expression of the 8 Gy leads to expression of the hematopoietic syndromehematopoietic syndrome

Dose limiting organ is the bone marrowDose limiting organ is the bone marrow

Again have sterilization of precursor cells, leading to Again have sterilization of precursor cells, leading to diminished supply of mature blood cellsdiminished supply of mature blood cells

Critical period not seen for several weeks, due to lag between Critical period not seen for several weeks, due to lag between the natural turnthe natural turn--over time of the mature cells and subsequent over time of the mature cells and subsequent inadequate supply from reduced precursor cell population.inadequate supply from reduced precursor cell population.

Hematopoietic SyndromeHematopoietic Syndrome

Peak incidence of death from hematopoietic Peak incidence of death from hematopoietic syndrome occurs at ~ 30 days after exposuresyndrome occurs at ~ 30 days after exposure

Death can be observed up to 60 days Death can be observed up to 60 days

Thus, express LDThus, express LD5050 for humans as LDfor humans as LD50/6050/60

Dose appears to be in the order of 4 GyDose appears to be in the order of 4 Gy

Hematopoietic Syndrome: Hematopoietic Syndrome: Experimental DataExperimental Data

Treatment of Radiation Treatment of Radiation Accident VictimsAccident Victims

Treatment options depend on exposure doseTreatment options depend on exposure dose

< 4< 4--5 Gy: 5 Gy:

ObservationObservationTreat specific symptoms e.g., antibiotics Treat specific symptoms e.g., antibiotics for infectionsfor infectionsBlood transfusions if requiredBlood transfusions if required

Treatment of Radiation Treatment of Radiation Accident VictimsAccident Victims

Dose > 5 Gy:Dose > 5 Gy:

Person will likely die from hematopoietic syndrome if Person will likely die from hematopoietic syndrome if untreateduntreated

Use antibiotics and keep patient in isolation to prevent Use antibiotics and keep patient in isolation to prevent infection infection

Animal studies suggest using antibiotics can increase LDAnimal studies suggest using antibiotics can increase LD5050twofold twofold

Aim to provide time for the bone marrow to regenerateAim to provide time for the bone marrow to regenerate

Treatment of Radiation Treatment of Radiation Accident VictimsAccident Victims

Can also give bone marrow transplants:Can also give bone marrow transplants:Results appear controversial, appears to be a very narrow therapResults appear controversial, appears to be a very narrow therapeutic eutic window, between 8window, between 8--10 Gy10 Gy

BMT after Chernobyl AccidentBMT after Chernobyl AccidentFollowing Chernobyl accident, 202 persons were admitted to Following Chernobyl accident, 202 persons were admitted to Clinical Hospital 6 in Moscow within 4 days of explosionClinical Hospital 6 in Moscow within 4 days of explosion

105 received an estimated total105 received an estimated total--body dose of body dose of ≥≥11--2 Gy2 Gy

33 initially considered to have received a dose of 33 initially considered to have received a dose of ≥≥6 Gy and 6 Gy and were potential candidateswere potential candidates

8 subsequently excluded when cytogentic analyses indicated 8 subsequently excluded when cytogentic analyses indicated probable doses of < 6 Gy (7 recovered, 1 died from skin burns)probable doses of < 6 Gy (7 recovered, 1 died from skin burns)

BMT after Chernobyl AccidentBMT after Chernobyl Accident

10 persons who received dose 10 persons who received dose ≥≥6 Gy excluded 6 Gy excluded due to extensive nonhemataologic damage, due to extensive nonhemataologic damage, mainly burns mainly burns

Remaining 15: 1 received a fetal liver rather Remaining 15: 1 received a fetal liver rather than BMT, 1 refused, 13 received BMT 4than BMT, 1 refused, 13 received BMT 4--16 16 days after the accidentdays after the accident

BMT after Chernobyl AccidentBMT after Chernobyl Accident

Only 2/13 (doses of 5.8 and 9.0 Gy) survived, began Only 2/13 (doses of 5.8 and 9.0 Gy) survived, began regenerating their own bone marrow on day 28 regenerating their own bone marrow on day 28

5 died mainly from burns, although 3 had GI damage and 1 5 died mainly from burns, although 3 had GI damage and 1 radiation pneumonitisradiation pneumonitis

3 died mainly from radiation pneumonitis 3 died mainly from radiation pneumonitis

2 died from graft2 died from graft--versusversus--host disease host disease

1 died from acute renal failure and adult respiratory distress 1 died from acute renal failure and adult respiratory distress syndrome.syndrome.

Growth Factor Stimulation of Bone Growth Factor Stimulation of Bone Marrow ProliferationMarrow Proliferation

PostPost--irradiation stimulation of cell proliferation in the irradiation stimulation of cell proliferation in the bone marrow predicted to be advantageous > 40 years bone marrow predicted to be advantageous > 40 years ago by Lajtha (1960)ago by Lajtha (1960)

Recent animal experiments using hematopoietic Recent animal experiments using hematopoietic growth factors and the clinical experience from the growth factors and the clinical experience from the treatment of accidental radiation exposure in Goiania, treatment of accidental radiation exposure in Goiania, Brazil (1987) are supportive of this farsighted Brazil (1987) are supportive of this farsighted predictionprediction

Goiania AccidentGoiania Accident

September 13 1987, Goiania, Central BrazilSeptember 13 1987, Goiania, Central Brazil

Approx 250 people exposed to a Approx 250 people exposed to a 137137Cs source Cs source from an abandoned RT unitfrom an abandoned RT unit

14 individuals showed bone marrow 14 individuals showed bone marrow depression, 8 developed acute radiation depression, 8 developed acute radiation syndromesyndrome

Goiania AccidentGoiania Accident

8/14 received GM8/14 received GM--CSF ivCSF iv

None received BMTNone received BMT

GMGM--CSF treatment not started until 23CSF treatment not started until 23--48 days after 48 days after initial and 19initial and 19--37 days after final exposure37 days after final exposure

4 died from hemorrhage and infection4 died from hemorrhage and infection